The proposed work is directed at an attempt to more fully understand the underlying molecular biology in thrombosis and hemorrhagic diseases. The specific area of attention is the blood coagulation mechanisms. The main aim is to find out about the covalent structure of bovine prothrombin. The amino acid sequence of P fragment, R fragment and O fragment are to be determined. Their respective molecular weights are 6,000, 16,000, and 10,000. When the amino acid sequence of each one is known the amino acid sequence of prothrombin will be known. Crystalline bovine thrombin is to be prepared for finding the tertiary structure by x-ray diffraction analysis. During prothrombin activation esterase activity arises, then fibrinogen clotting activity. The latter then disappears while esterase activity persists. These facts are to be explained in terms of underlying structural studies. Attempts to isolate esterase thrombin and obtain crystals are to be made. In comparative studies plans are to obtain similar information with human prothrombin and thrombin. This information is to be extended to obtain an idea about the structure of coagulase thrombin. The latter has peculiar activities. Information is to be obtained on the properties of purified bovine Ac-globulin, and in immunological studies the properties of purified clotting components are to be tested. Lastly, synthetic polypeptides are to be designed, synthesized, and studied as substrates and inhibitors of thrombin.